Despite the magnitude of the afflicted population and the potential for combined gestational alcohol consumption and maternal hypertension, few studies have been directed towards this interaction. We propose to study the basic mechanisms which modulate maternal-fetal response to gestational alcohol consumption during hypertensive pregnancy. Hypertensive rats consuming ethanol during pregnancy have an exaggerated hypertensive response and the prebirthing hypotensive phase is abolished by ethanol. This leads to significant reproductive loss and increase fetal anomalies. We believe these observations to be significant and worth of more detailed studies. Our goal is to elucidate the mechanisms of interaction between ethanol consumption and elevated gestational blood pressures in mechanisms of interaction between ethanol consumption and elevated gestational blood pressures in SHR. The principal hypothesis is that placental dysfunction is the cause of exaggerated hypertensive response to gestational ethanol consumption. WE will determine if structural changes in the placenta are associated with disturbances in blood flow. We will determine if isolated uterine artery vascular reactivity changes during gestation and what the effects of hypertension and ethanol consumption are upon this model system. We will determine whether ethanol consumption is accompanied by alterations in placental aromatase activity, or whether blood and tissue levels of sex steroids, prostaglandins or thromboxane are affected by alcohol and hypertension during pregnancy. Thus our specific aims are: 1. Refine our initial findings in SHR and WKY rats by addition of a pair - fed, liquid diet, isocaloric replacement design. 2. Critically evaluate the structural and functional consequences of maternal ethanol consumption and spontaneous hypertension on the placenta, and its relationship to regional blood flow and to uterine artery vascular reactivity. 3. Determine whether sex steroids or prostanoids ar implicated in the exaggerated gestational hypertensive response to ethanol. In these studies we will measure maternal blood and placental levels of progesterone, testosterone and estradiol by radioimmunoassay at critical points during gestation. Placental aromatase activity will be determined. Prostaglandin and thromboxane in the blood and placental will be determined by radioimmunoassay. 4. We will determine the contractile sensitivity of isolated uterine arteries from hypertensive, normotensive and alcohol - consuming rats to vasoconstrictor agents and to prostaglandin and thromboxane agonists; and to prostaglandin receptor blocking drugs and cyclooxygenase inhibitors. 5. In separate studies, we will directly determine whether exogenous progesterone will re-establish the periparturition hypotension and prevent alcoholic, hypertensive embryopathy. The proposed studies are significant in that they will contribute to an understanding of the interaction between two common human reproductive risk factors and they will increase our understanding of the mechanisms involved in the exacerbation of spontaneous hypertension by alcohol.